Very interesting observations have been made (see DA00362-03 grant application) on the augmenting effect of morphine sulfate on the single neuron activity in the amyglaloid nucleus of the cat. The spontaneous and evoked activity is not readily reversed by naloxone, whereas benzodiazepines, such as chlordiazepoxide, diazepam, etc., are very potent antagonists. Currently we are studying neurons in the hippocampus, which reacts to naloxone somewhat differently, though benzodiazepines are even more effective. We plan to continue these studies to include some other neurons in the entire limbic system. It is planned to apply the drug antagonism by the microiontophoretic technique. Hypothalamus is of particular interest since the ventromedial nucleus (VMN) is known to have extensive anatomic connections with the amygdala. It has been claimed that VMN is essential in the manifestations of tolerance and addiction. A project using the operant behavioral technique is planned to investigate addiction problems. Other parts of the limbic system will also be investigated for physical dependence. Finally we are also interested in renewing our investigation on the mechanism of mydriasis induced by morphine in the cat. Microiontophoretic technique will also be used whenever it is feasible.